title: Crystallization of a new polymorph of acetohexamide from 2-hydroxybutyl-β-cyclodextrin solution: form VI with a high aqueous solubility.
abstract: A new polymorph of acetohexamide (Form VI) was prepared via the formation of a complex with 2-hydoxybutyl-β-cyclodextrin (HB-β-CD) in aqueous solution. An alkaline solution of acetohexamide and HB-β-CD was adjusted to pH 4.0 by titration with hydrochloric acid. The resulting opaque solution was filtered through paper and allowed to stand at 4°C for 24h. The resulting precipitate was isolated on a filter and analyzed for polymorph content by powder X-ray diffractometry and thermal analysis. The diffraction pattern and thermal behavior of the precipitate was different from those of previously reported acetohexamide polymorphs (Forms I, III, IV and V), indicating that a new polymorph of the drug, i.e. Form VI was produced. This new polymorph was fairly stable against conversion to a stable form even at accelerated storage conditions. Crystalline Form VI was highly soluble in water and dissolved more rapidly than the other known polymorphs. This property was reflected in the blood concentrations of the drug after oral administration to rats.
authors.affiliation: Faculty of Pharmacy, King Abdulaziz University, 80260, Jeddah 21589, Saudi Arabia.
authors.forename: Hibah
authors.initials: H
authors.lastname: Aldawsari
authors.forename: Abdulmalik
authors.initials: A
authors.lastname: Altaf
authors.forename: Zainy M
authors.initials: ZM
authors.lastname: Banjar
authors.forename: Daisuke
authors.initials: D
authors.lastname: Iohara
authors.forename: Mami
authors.initials: M
authors.lastname: Nakabayashi
authors.forename: Makoto
authors.initials: M
authors.lastname: Anraku
authors.forename: Kaneto
authors.initials: K
authors.lastname: Uekama
authors.forename: Fumitoshi
authors.initials: F
authors.lastname: Hirayama
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000092:Acetohexamide / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D003460:Crystallization; D007004:Hypoglycemic Agents / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D008297:Male; D033362:Powder Diffraction; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D014961:X-Ray Diffraction; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D007004:Hypoglycemic Agents; D047392:beta-Cyclodextrins; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000092:Acetohexamide
keywords: 2-Hydroxybutyl-β-cyclodextrin; Acetohexamide; Dissolution rate; In vivo-absorption; New polymorph